Morrison Rachel, Gardiner Chris, Evidente Antonio, Kiss Robert, Townley Helen
Department of Engineering Science, Oxford University, Parks Road, Oxford, UK.
Pharm Res. 2014 Oct;31(10):2904-17. doi: 10.1007/s11095-014-1386-3. Epub 2014 May 3.
To design and synthesize chemoembolization particles for the delivery of Ophiobolin A (OphA), a promising fungal-derived chemotherapeutic, directly at the tumour location. To investigate cell death mechanism of OphA on a Rhabdomyosarcoma cancer (RD) cell line. Rhabdomyosarcoma is the most common soft tissue sarcoma in children; with a 5-year survival rate of between 30 and 65%.
Multimodal chemoembolization particles were prepared by sintering mesoporous silica nanoparticles, prepared by the sol-gel method, onto the surface of polystyrene microspheres, prepared by suspension copolymerisation. The chemoembolization particles were subsequently loaded with OphA. The effects of OphA in vitro were characterised by flow cytometry and nanoparticle tracking analysis (NanoSight).
High loading of OphA onto the chemoembolization particles was achieved. The subsequent release of OphA onto RD cells in culture showed a 70% reduction in cell viability. OphA caused RD cells to round up and their membrane to bleb and caused cell death via apoptosis. OphA caused both an increase in the number of microvesicles produced and an increase in DNA content within these microvesicles.
The prepared chemoembolization particles showed good efficacy against RD cells in culture.
设计并合成化学栓塞颗粒，用于将蛇孢菌素A（OphA），一种有前景的真菌衍生化疗药物，直接递送至肿瘤部位。研究OphA对横纹肌肉瘤癌细胞（RD）细胞系的细胞死亡机制。横纹肌肉瘤是儿童中最常见的软组织肉瘤；5年生存率在30%至65%之间。
通过将溶胶 - 凝胶法制备的介孔二氧化硅纳米颗粒烧结到悬浮共聚法制备的聚苯乙烯微球表面，制备多模态化学栓塞颗粒。随后将OphA负载到化学栓塞颗粒上。通过流式细胞术和纳米颗粒跟踪分析（NanoSight）表征OphA在体外的作用。
实现了OphA在化学栓塞颗粒上的高负载。随后OphA在培养的RD细胞上的释放显示细胞活力降低了70%。OphA使RD细胞变圆，细胞膜起泡，并通过凋亡导致细胞死亡。OphA导致产生的微泡数量增加以及这些微泡内的DNA含量增加。
制备的化学栓塞颗粒在培养中对RD细胞显示出良好的疗效。
